Igor Marchetti

The Default Mode Network and Recurrent Depression: A Neurobiological Model of Cognitive Risk Factors

A neurobiological account of cognitive vulnerability for recurrent depression is presented based on recent developments of resting state neural networks. We propose that alterations in the interplay between task positive (TP) and task negative (TN) elements of the Default Mode Network (DMN) act as a neurobiological risk factor for recurrent depression mediated by cognitive mechanisms. In the framework, depression is characterized by an imbalance between TN-TP components leading to an overpowering of TP by TN activity. The TN-TP imbalance is associated with a dysfunctional internally-focused cognitive style as well as a failure to attenuate TN activity in the transition from rest to task. Thus we propose the TN-TP imbalance as overarching neural mechanism involved in crucial cognitive risk factors for recurrent depression, namely rumination, impaired attentional control, and cognitive reactivity. During remission the TN-TP imbalance persists predisposing to vulnerability of recurrent depression. Empirical data to support this model is reviewed. Finally, we specify how this framework can guide future research efforts.

Accelerated HF-rTMS in treatment-resistant unipolar depression: Insights from subgenual anterior cingulate functional connectivity

Abstract Objectives. Intensified repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) may result in fast clinical responses in treatment resistant depression (TRD). In these kinds of patients, subgenual anterior cingulate cortex (sgACC) functional connectivity (FC) seems to be consistently disturbed. So far, no de novo data on the relationship between sgACC FC changes and clinical efficacy of accelerated rTMS were available. Methods. Twenty unipolar TRD patients, all at least stage III treatment resistant, were recruited in a randomized sham-controlled crossover high-frequency (HF)-rTMS treatment study. Resting-state (rs) functional MRI scans were collected at baseline and at the end of treatment. Results. HF-rTMS responders showed significantly stronger resting-state functional connectivity (rsFC) anti-correlation between the sgACC and parts of the left superior medial prefrontal cortex. After successful treatment an inverted relative strength of the anti-correlations was observed in the perigenual prefrontal cortex (pgPFC). No effects on sgACC rsFC were observed in non-responders. Conclusions. Strong rsFC anti-correlation between the sgACC and parts of the left prefrontal cortex could be indicative of a beneficial outcome. Accelerated HF-rTMS treatment designs have the potential to acutely adjust deregulated sgACC neuronal networks in TRD patients.

Mindwandering heightens the accessibility of negative relative to positive thought.

Mindwandering (MW) is associated with both positive and negative outcomes. Among the latter, negative mood and negative cognitions have been reported. However, the underlying mechanisms linking mindwandering to negative mood and cognition are still unclear. We hypothesized that MW could either directly enhance negative thinking or indirectly heighten the accessibility of negative thoughts. In an undergraduate sample (n=79) we measured emotional thoughts during the Sustained Attention on Response Task (SART) which induces MW, and accessibility of negative cognitions by means of the Scrambled Sentences Task (SST) after the task. We also measured depressive symptoms and rumination. Results show that in individuals with elevated levels of depressive symptoms MW during SART predicts higher accessibility of negative thoughts after the task, rather than negative thinking during the task. These findings contribute to our understanding of the underlying mechanisms of MW and provide insight into the relationship between task-involvement and affect.

Self-generated thoughts and depression: from daydreaming to depressive symptoms

Human minds often engage in thoughts and feelings that are self-generated rather than stimulus-dependent, such as daydreaming. Recent research suggests that under certain circumstances, daydreaming is associated with adverse effects on cognition and affect. Based on recent literature about the influence of resting mind in relation to rumination and depression, this questionnaire study investigated mechanisms linking daydreaming to depressive symptoms. Specifically, an indirect effect model was tested in which daydreaming influences depressive symptoms through enhancing self-focus and ruminative thought. Results were in line with the hypothesis and several alternative pathways were ruled out. The results provide initial supportive evidence that daydreaming can influence depressive symptoms through influences on self-focus and rumination. Further research should use prospective or experimental designs to further validate and strengthen these conclusions.

The interplay between cognitive risk and resilience factors in remitted depression: A network analysis

BACKGROUND Individuals in remission from depression are at increased risk for developing future depressive episodes. Several cognitive risk- and resilience factors have been suggested to account for this vulnerability. In the current study we explored how risk- and protective factors such as cognitive control, adaptive and maladaptive emotion regulation, residual symptomatology, and resilience relate to one another in a remitted depressed (RMD) sample. METHODS We examined the relationships between these constructs in a cross-sectional dataset of 69 RMD patients using network analyses in order to obtain a comprehensive, data-driven view on the interplay between these constructs. We subsequently present an association network, a concentration network, and a relative importance network. RESULTS In all three networks resilience formed the central hub, connecting perceived cognitive control (i.e., working memory complaints), emotion regulation, and residual symptomatology. The contribution of the behavioral measure for cognitive control in the network was negligible. Moreover, the directed relative importance network indicates bidirectional influences between these constructs, with all indicators of centrality suggesting a key role of resilience in remission from depression. LIMITATIONS The presented findings are cross-sectional and networks are limited to a fixed set of key constructs in the literature pertaining cognitive vulnerability for depression. CONCLUSIONS These findings indicate the importance of resilience to successfully cope with stressors following remission from depression. Further in-depth studies will be essential to identify the specific underlying resilience mechanisms that may be key to successful remission from depression.

Spontaneous Thought and Vulnerability to Mood Disorders The Dark Side of the Wandering Mind

There is increasing interest in spontaneous thought, namely task-unrelated or rest-related mental activity. Spontaneous thought is an umbrella term for processes like mind-wandering, involuntary autobiographical memory, and daydreaming, with evidence elucidating adaptive and maladaptive consequences. In this theoretical framework, we propose that, apart from its positive functions, spontaneous thought is a precursor for cognitive vulnerability in individuals who are at risk for mood disorders. It is important that spontaneous thought mostly focuses on unattained goals and evaluates the discrepancy between current and desired status. In individuals who stably (i.e., trait negative affectivity) or transitorily (i.e., stress) experience negative emotions in reaction to goal-discrepancy, spontaneous thought fosters major cognitive vulnerabilities (e.g., rumination, hopelessness, low self-esteem, and cognitive reactivity), which, in turn, enhance depression. Furthermore, we also highlight preliminary links between spontaneous thought and bipolar disorder. The evidence for this framework is reviewed, and we discuss theoretical and clinical implications of our proposal.

Rest-Related Dynamics of Risk and Protective Factors for Depression A Behavioral Study

Resting state provides an important condition to study depressogenic cognition because neuropsychological studies have indicated that rest is associated with heightened self-related processing. We examined relationships between rest-related internal focus, cognitive reactivity (vs. mindfulness), rumination, and negative mood outside the functional magnetic resonance imaging scanner in an undergraduate sample (N = 80). We tested a theory-based effect by which, in the presence of cognitive risk (vs. protective) factors, internal focus lowers mood via ruminative self-focus. Such an effect was detected in individuals with high cognitive reactivity, whereas brooding showed only an incremental effect. However, this dynamic was not significant in individuals with low cognitive reactivity, despite the level of brooding, or high mindfulness. These results provide an important window on risk for depressogenic thought during resting state.

Manipulating cues in mind wandering: Verbal cues affect the frequency and the temporal focus of mind wandering

Our understanding of mind wandering (MW) has dramatically increased over the past decade. A key challenge still facing research is the identification of the processes and events that directly cause and control its occurrence. In the present study we sought to shed light on this question, by investigating the effects of verbal cues on the frequency and temporal focus of MW. To this aim, we experimentally manipulated the presence of irrelevant verbal cues during a vigilance task, in two independent groups (Verbal-cues group vs. No-cues group). We found that compared to the No-cues group, the Verbal-cues group reported a higher amount of MW, mostly triggered by the irrelevant cue-words, and a higher proportion of past-oriented MW compared to the other temporal orientations. These results demonstrate that task-irrelevant verbal stimulation increases the frequency of MW and steers its temporal orientation toward the past. Implications for the research on MW are discussed.

Examining the Relation Between Mood and Rumination in Remitted Depressed Individuals A Dynamic Systems Analysis

Cognitive theories of recurrent depression suggest that the relationship between mood and cognition is altered by previous depressive episodes. In individuals remitted from depression (RMD) this would be linked to a larger susceptibility for new depressive symptoms. This study explored whether the association between mood and rumination indeed is different between RMD and nondepressed controls relying on dynamic systems theory (DST). From DST we selected entropy, defined here as the level of unpredictability in the relation between mood and rumination, as the main variable of interest. Daily electronic dairy measures of mood and rumination were administered in 31 RMD patients and 32 healthy controls. The results indicate that mean levels of rumination and negative mood were elevated in RMD compared with controls. At the group level, entropy did not differ significantly and entropy was also not associated with the number of episodes. However, entropy predicted depressive symptoms in the RMD group and the brooding subtype of rumination in both groups at the 6-month follow-up. These data are specific for entropy and were not obtained using mean levels of momentary mood and rumination.

Unveiling the Structure of Cognitive Vulnerability for Depression: Specificity and Overlap

There is extensive literature establishing the influence of rumination, hopelessness, and dysfunctional attitudes on depressive symptoms. However, it is unclear whether these vulnerability factors are distinctly related to depressive symptoms or show substantial overlap. In two large samples of undergraduates (Study #1, n = 304; Study #2, n = 491) and two samples of clinically depressed individuals (Study #3, n = 141; Study #4, n = 109, from published studies), questionnaire data were used to examine the relationship between cognitive vulnerability factors and depressive symptoms, along with additional measures of anxiety and stress symptoms. To decompose model fit into its specific and common partitions, we relied on commonality analysis (CA). CA showed that there is substantial overlap in cognitive risk factors for depression. Moreover, we found strong evidence that hopelessness provides a unique statistical contribution to depression. This pattern of findings was stable in healthy as well as clinical samples. Symptom-levels analysis revealed that a specific subset of depressive symptoms are associated with hopelessness. In closing, we showed that CA provides a powerful tool to map unique and overlapping variance between multiple risk factors. Moreover, hopelessness emerged to be an important focus of clinical attention.